4MQW

Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor (P31)

Summary for 4MQW

• Entry DOI: 10.2210/pdb4mqw/pdb
• Related: 4ay9
• Descriptor: Glycoprotein hormones, alpha polypeptide, Follitropin subunit beta, Follicle-stimulating hormone receptor, ... (7 entities in total)
• Functional Keywords: cystine-knot, leucine-rich repeats, glycoprotein hormone, gpcr, sulfation, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 199817.15

Authors

Jiang, X.,Liu, H.,Chen, X.,He, X. (deposition date: 2013-09-16, release date: 2014-04-09, Last modification date: 2024-11-06)

Primary citation

Jiang, X.,Fischer, D.,Chen, X.,McKenna, S.D.,Liu, H.,Sriraman, V.,Yu, H.N.,Goutopoulos, A.,Arkinstall, S.,He, X.
Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer.
J.Biol.Chem., 289:14273-14282, 2014

PubMed Abstract: Follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor, is an important drug target in the development of novel therapeutics for reproductive indications. The FSHR extracellular domains were observed in the crystal structure as a trimer, which enabled us to propose a novel model for the receptor activation mechanism. The model predicts that FSHR binds Asnα(52)-deglycosylated FSH at a 3-fold higher capacity than fully glycosylated FSH. It also predicts that, upon dissociation of the FSHR trimer into monomers, the binding of glycosylated FSH, but not deglycosylated FSH, would increase 3-fold, and that the dissociated monomers would in turn enhance FSHR binding and signaling activities by 3-fold. This study presents evidence confirming these predictions and provides crystallographic and mutagenesis data supporting the proposed model. The model also provides a mechanistic explanation to the agonist and antagonist activities of thyroid-stimulating hormone receptor autoantibodies. We conclude that FSHR exists as a functional trimer.

PubMed: 24692546
DOI: 10.1074/jbc.M114.549592

Experimental method

X-RAY DIFFRACTION (2.9 Å)